Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains: [Inkl. Correction]
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Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84–98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.
Original language | English |
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Journal | Nature Genetics |
Volume | 55 |
Pages (from-to) | 198–208 |
Number of pages | 18 |
ISSN | 1061-4036 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Correction: 10.1038/s41588-023-01350-w
Link: https://www.nature.com/articles/s41588-023-01350-w
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
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